1. Field
The present disclosure relates to polypeptides inhibiting binding between vascular endothelial growth factor receptor-2 and a vascular endothelial growth factor, fusion proteins including the polypeptides, and a method of preparing the fusion proteins.
2. Description of the Related Art
Angiogenesis is a process involving growth of new blood vessels from existing vessels, which plays a vital role in formation of organs, normal biological growth, and wound healing. In addition, abnormal angiogenesis is known to be an important contributor to diseases such as development and metastasis of tumor cells, age-related macular degeneration, diabetic retinopathy, psoriasis, rheumatoid arthritis, and chronic inflammation.
The development and metastasis of tumor cells depend on angiogenesis. Thus, since a hypothesis in which anti-angiogenesis therapeutic drugs would become novel anti-cancer therapeutic drugs was proposed, research into the mechanism of angiogenesis has been conducted to develop a new anti-cancer therapeutic drug. Among various angiogenesis factors, research into the function of vascular endothelial growth factor (VEGF) has been most actively conducted. When tumor tissues develop, the tumor tissues cause vessel regression and the tumor tissues are excessively grown to form a hypoxic environment therein. As a result, conditions at which angiogenesis occurs are provided within tumor tissue. Under these conditions, vascular endothelial cells increase expression of VEGF to form new vessels around tumor cells. Since the growth of the vascular endothelial cells and vascular formation are induced by expression of VEGF and reaction between VEGF and its receptor, the reactions described above are a vital process in angiogenesis. Thus, angiogenesis in tumor tissue is suppressed by inhibiting binding between the vascular endothelial growth factor receptor (VEGFR) and VEGF, and a compound that inhibits binding between VEGFR and VEGF may become an anti-cancer drug candidate or provide a target for developing anti-cancer therapies. In addition, VEGFR may emerge as a target for effective anti-cancer therapies since VEGFR is a protein, which initiates transduction of intracellular signals of vascular formation.
Although an inhibitor of VEGFR tyrosine kinase is known, in clinical trials this inhibitor was shown to be thromboembolic and severely toxic.